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桑根醇 L 通过激活半胱氨酸天冬氨酸蛋白酶级联和凋亡诱导因子促进黑色素瘤皮肤癌细胞的凋亡。

Sanggenol L promotes apoptotic cell death in melanoma skin cancer cells through activation of caspase cascades and apoptosis-inducing factor.

机构信息

Department of Biotechnology, Dong-A University, Busan, 49315, Republic of Korea.

Department of Biotechnology, Dong-A University, Busan, 49315, Republic of Korea.

出版信息

Food Chem Toxicol. 2020 Apr;138:111221. doi: 10.1016/j.fct.2020.111221. Epub 2020 Feb 19.

DOI:10.1016/j.fct.2020.111221
PMID:32084496
Abstract

Sanggenol L is one component of root bark of Morus alba. The molecular and cellular mechanisms of sanggenol L effects on melanoma cells are not well known. Recently, melanoma is the most common skin cancer with a high mortality rate not only in United States, but also in East Asia. Therefore, safe and effective treatments for melanoma treatment are required. In this study, we investigated whether or not sanggenol L possesses anti-cancer activity in human and mouse melanoma skin cancer cells. Sanggenol L treatment exerted significant cell growth inhibitory effects and inhibited colony formation capacity against B16, SK-MEL-2, and SK-MEL-28 melanoma skin cancer cells, whereas HaCaT human epithelial keratinocyte cells was unaffected by sanggenol L treatment. Sanggenol L treatment resulted in apoptotic cell death in melanoma skin cancer cells, which was characterized by accumulation of apoptotic cells, nuclear condensation, and apoptotic bodies. We also showed that sanggenol L treatment induced caspase-dependent apoptosis (up-regulation of Bax and cleaved-PARP or down-regulation of Bid, Bcl-2, procaspse-3, -8, and -9), induction of caspase-independent apoptosis (up-regulation of AIF and Endo G on cytosol) in melanoma skin cancer cells. These results suggest that sanggenol L induces caspase-dependent and -independent apoptosis in melanoma skin cancer cells.

摘要

桑根醇 L 是桑科植物桑白皮的一种成分。桑根醇 L 对黑素瘤细胞的分子和细胞机制尚不清楚。最近,黑色素瘤不仅在美国,而且在东亚也是最常见的皮肤癌,死亡率很高。因此,需要安全有效的治疗方法。在这项研究中,我们研究了桑根醇 L 是否对人源和鼠源黑素瘤皮肤癌细胞具有抗癌活性。桑根醇 L 处理对 B16、SK-MEL-2 和 SK-MEL-28 黑素瘤皮肤癌细胞的生长有明显的抑制作用,并抑制集落形成能力,而 HaCaT 人上皮角质形成细胞不受桑根醇 L 处理的影响。桑根醇 L 处理导致黑素瘤皮肤癌细胞发生凋亡性细胞死亡,其特征为凋亡细胞的积累、核浓缩和凋亡小体。我们还表明,桑根醇 L 处理诱导 caspase 依赖性凋亡(Bax 和 cleaved-PARP 的上调或 Bid、Bcl-2、procaspase-3、-8 和 -9 的下调),诱导 caspase 非依赖性凋亡(AIF 和 Endo G 在细胞质中的上调)在黑素瘤皮肤癌细胞中。这些结果表明,桑根醇 L 诱导黑素瘤皮肤癌细胞发生 caspase 依赖性和非依赖性凋亡。

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